My interest in investigating the innate and adaptive immune responses to bacterial infections was strengthened by a series of fascinating observations I made while working with Borrelia hermsii bacteremia system. I found a previously unrecognized function of B1b lymphocytes, a minor subset of mature B cells, in long-lasting T cell-independent (TI) B cell memory responses. This seminal finding on B1b cells has been recapitulated using several important human pathogens such as Streptococcus pneumoniae and Salmonella enterica serovar Typhi (S. Typhi). The antigens recognized by B1b cells in these bacterial systems include not only bacterial outer-membrane proteins but also polysaccharides, which are attractive vaccine candidates. In fact, the capsular polysaccharides of both S. pneumoniae (Pneumovax®23) and S. Typhi (Typhim Vi®) are the protective targets in the current vaccines against pneumococcal diseases and typhoid, respectively, in humans. However, these vaccines, like any other bacterial polysaccharide vaccines, have two major drawbacks. First, they do not induce optimal antibody responses in infants and young children. Second, while they induce a response in older children and adults, they do not generate B cell memory, and therefore the protection conferred by the polysaccharide vaccines is short-lived.
Since we found that bacterial exposure induces efficient B1b cell memory, but not isolated polysaccharides that are in the present vaccines we are trying to understand the molecular and cellular basis involved in the generation of polysaccharide-specific B cell memory.
Molecular basis for T cell-independent B cell memory to bacterial polysaccharide vaccines
Antibody-mediated effector mechanisms that control of polysaccharide-encapsulated bacteria
B cell receptor/antibody repertoire early and later in life, and its impact on polysaccharide vaccines. Collaborator: Drs. John F. Kearney and Andreas Baumler
Human Immune System mice as a translational platform to identify impaired anti-polysaccharide responses in human infants, and those individuals underwent bone marrow transplantation. Collaborators: Drs. Tim Manser, Neal Flomenberg and Lori Grosso
Collaborative Cross mice to evaluate the novel polysaccharide vaccines and adjuvants against Salmonella Typhi, a human-restricted bacterial pathogen. Collaborators: Drs. Linda Siracusa, Fernando Pardo-Manuel de Villena and Andreas Baumler
Cellular and molecular basis for the pathogenesis of neuroborreliosis. Collaborator: Dr. Hongqi Liu